The present invention relates to novel methods for predicting suicidal and other abnormal behaviors. In particular, it relates to the detection of polymorphisms in the tryptophan hydroxylase gene, which are correlated with abnormal serotonergic function and related behaviors.
Genetic factors have been implicated in the etiology of alcoholism, violence, and suicide in both family and twin studies. A strong interrelationship exists between these phenotypes, as they tend to occur in the same individual and in individuals who are genetically closely related. Although these disorders are heterogeneous in their clinical expression, and have complex causes, it is possible to identify more homogeneous subgroups among patients with these problems.
Decreased brain serotonin concentration has been associated with several behavioral traits including impulsive, aggressive and suicidal behavior, pyromania (fire setting), and with disruption of circadian rhythms. For a review of the correlation between serotonin concentrations and abnormal behavior see, Lopez-Ibor et al. (1991) In Serotonin-related psychiatric syndromes: clinical and therapeutic links (Ed. Cassano and Akiskal, Royal Society of Medicine Services Ltd.) pp. 35-40. Serotonergic activity is correlated with the concentration of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (Asberg et el. (1976) Arch. Gen. Psychiatry 33: 1193-1197).
Low concentrations of 5-HIAA in the cerebrospinal fluid (CSF) have been associated with behaviors characterized by intolerance to delay, or impulsive behavior. These include impulsive aggression (including homicide), pyromania (fire setting), personality disorders, and alcoholism. Serotonin is also critical in slow-wave sleep, temperature control, and appetitive behaviors. Diminished CSF 5-HIAA concentrations have been found to be associated with risk of suicide in depressed patients. In animal studies, indices of decreased serotonin concentrations are connected with postulated anxiety-related intolerance to delay and deficient control of impulses.
Although 5-HIAA concentrations in CSF are correlated with abnormal serotonergic behaviors, 5-HIAA's usefulness as a marker is limited by the difficulty in obtaining CSF. CSF may only be obtained by an invasive, expensive, and impractical procedure. Thus, there is a need for an easily typed marker that is correlated with 5-HIAA levels and abnormal serotonergic behaviors. The present invention fulfills this and other needs.